The beta-lactam antibiotics are perhaps the most widely used and studied antibiotics. The preparation of totally synthetic and semi-synthetic antibiotics is vital to the development of an understanding of the structural-function relationship of the beta-lactam antibiotics and the mode of action of the beta-lactamase enzymes of bacterial origin. While one of the most efficient and useful methods of preparation of the beta-lactam unit has been the cyclization of beta-haloamides, the strongly basic conditions required are often incompatible with the peripheral substitution for structural elaboration . An efficient synthesis of substituted 2-azetidinones, the core unit of the beta-lactam antibiotics, has been developed based on the cyclization of substituted beta-hydroxyhydroxamic acids. The key to the process is the low NH pK of the intermediate O-alkylhydroxamic acid which facilitates N-C4 bond closure under conditions milder than previously possible. Application of the methodology to the synthesis of appropriate antibiotics precursors under controlled conditions is now being pursued.